tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field</i>: Influenza A(H3N2) Outbreak Following a School Event — Los Angeles, California, March 2022
Authors: Lello Tesema, Dominique Sullivan, Marifi Pulido, Elizabeth Traub, Jose Escobar, Leo Moore, Nicole Green, Peera Hemarajata, Maria Cruely, Rachel Civen, Alicia El-Togby, Garin Ohannessian, Sylvia Silas, Rosita San Diego, Dawn Terashita, Sharon Balter, Prabhu Gounder
Journal: MMWR Morbidity and Mortality Weekly Report (2022)
Improving clinician knowledge of cancer-related anemia (CRA) and chemotherapy-induced anemia (CIA) through the execution of a hybrid educational initiative focused on the evolving role of intravenous iron.
Authors: Bryan Carson Taylor, George M. Rodgers, Susan H. Gitzinger, Tina Trieu, Vanessa Carranza, Jessica Hall, Rebecca Weaver
Journal: Journal of Clinical Oncology (2022)

e23001 Background: Anemia is an extremely common and robustly deleterious complication experienced by patients with cancer, with impacts ranging from patient-reported quality-of-life metrics, to functional capacity, to morbidity and mortality implications. Cancer-related anemia (CRA) and chemotherapy-induced anemia (CIA) arise from a complex pathogenesis and are often associated with multifactorial etiology, but iron deficiency (ID) is an especially prominent genesis in these patients and is a preeminent clinical focus for hematology/oncology clinicians, not only because of its frequency, but also because it is directly treatable and reversible. Recent positive data readouts examining intravenous iron as a mechanism to improve anemia outcomes in comorbid oncologic states illustrates a compelling and exigent need to educate the hematology/oncology clinicians managing patients with cancer. These clinicians are optimally positioned to ensure improved CRA/CIA patient outcomes. That was the formative objective of this educational initiative. Methods: We conducted a 180-minute symposium at the 2021 American Society of Hematology (ASH) Annual Meeting, with a panel of 5 hematology/oncology experts. The activity was delivered live, in-person in Atlanta, and was also live streamed to a national and international audience on a virtual basis; the session was then provided as an online on-demand offering for those couldn’t attend the live meeting. Clinician knowledge metrics were evaluated from pre-activity to post-activity via audience response software (in-person) and Zoom polling (virtual); all test questions were directly correlated with activity learning objectives. Results: Across all 3 delivery modalities, the educational initiative reached a vast audience of nearly 8,000 learners. Meaningful knowledge advancements were achieved across each of the following clinical topics of emphasis (statistics reflect differential between pre-test and post-test performance): Diagnosis of CRA/CIA using clinical signs, symptoms, and laboratory diagnoses (+17%). Differentiation of functional vs. absolute iron deficiency (+33%). Identifying how elevated hepcidin levels impact iron supplementation strategies (+37%). Knowledge of improved safety profiles of next-generation IV iron products (+75%). Correctly evaluating the benefits of IV iron given a real-world CIA patient case (+33%). Conclusions: Our outcomes illustrate both the relatively low baseline knowledge of hematology/oncology clinicians related to CRA/CIA management and the transformative impact of timely educational programming. Ongoing educational efforts focused on this clinical topic and target audience are warranted.
Patient’s voice: perspective and persistence
Authors: Calum Johnston
Journal: British Journal of Sports Medicine (2022)

Throughout my younger years, I loved my football.No injuries, no pressure; just freedom and pleasure.However, the older I got, the taller I grew, and the stronger I became, the more complications I was faced with through injuries.In January 2020, after a long travel up to Aberdeen, Scotland, the pain in the front of my knee was just unbearable.This pain had bothered me for months before this game, but no one could put their finger on what it really was.I was just told to take weeks out and then try again.I really
MEDB-01. Management of the risk of medulloblastoma associated to familial adenomatous polyposis and dysregulated Wnt signalosome
Authors: Balkiss Abdelmoula, Fatma Abid, Amir Karra, Sonda Kammoun, Samir Aloulou, Nouha Bouayed Abdelmoula
Journal: Neuro-Oncology (2022)

Abstract APC is the key gene of the familial adenomatous polyposis (FAP). This tumor suppressor gene functions by negatively regulating the β-catenin protein and the majority of APC mutations disrupt the β-catenin degradation complex signalosome leading to the activation of the canonical Wnt pathway. Pathogenic APC mutations were reported in association to medulloblastoma. In this study, we report rare mutations of the APC gene detected in Tunisian families from the governorate of Sfax presenting clinically with various digestive and extra-digestive manifestations. Our goal was to assess the oncogenic risks encountered by our pediatric carriers to offer an accurate genetic counselling, particularly at the neurologic level. Molecular investigation of all members of two families was conducted, using bidirectional sequencing of all 15 exons of the APC gene. A phenotype-genotype correlation was conducted to elucidate the mutational pathophysiological mechanism. Two rare mutations were revealed in our familial study. The first mutation was located at exon 13 and was a missense mutation at codon 1690. The second mutation was a deletion identified at codon 4652 in exon 15. The mutations resulted both in truncated gene products. Clinical manifestations closely depending on the position of the mutation were respectively colic polyposis for the first mutation and soft tissue fibromatous tumors for the second. The localization of the APC mutations allows better targeting of surveillance for clinical manifestations that may be included in FAP. Mutations that remove the Axin-binding sites, as is the case for the first mutation, lead to severe clinical pictures whereas mutations that retain one or two of the Axin binding sites are associated with other features such as desmoid tumors. The risk of the Wnt- medulloblastoma subtype, higher among patients with FAP should be considered with a more awareness of signs and symptoms related to CNS tumors in the FAP context.
Expression of markers of epithelial-mesenchymal transition in various forms of vulvar cancer.
Authors: Elena P. Ulianova, Angelina V. Busarova, Natalya V. Porkhanova, Aleksandr B. Sagakyants, Natalia A. Petrusenko, Oksana G. Shulgina, Elena N. Chernikova, Svetlana M. Bakulina, Tatiana F. Pushkareva, Ekaterina V. Verenikina
Journal: Journal of Clinical Oncology (2022)

e17532 Background: Vulvar cancer is a rare gynecologic tumor accounting for 2–5% of all gynecologic cancers. The epithelial-mesenchymal transition (EMT) is considered one of the factors contributing to the aggressive behavior of vulvar squamous cell carcinoma. E- and N-cadherins are key regulators of this transition. The purpose of our study was to identify the features of the expression of EMT markers in vulvar cancer as prognostic factors. Methods: The study included 30 patients aged 39-70 years, mean age 52 years, with vulvar cancer: control group (n = 15) with vulvar cancer T 1-2 N 0 -M 0 (G2); main group (n = 15) with vulvar cancer T 1-2 N 1 -M 0 (G2) with metastases to inguinal lymph nodes. Immunohistochemical study was performed on sections from paraffin blocks of tumors using monoclonal mouse antibodies to E-cadherin (12#, Cloud-Clone Corp.) and N-cadherin (389, Invitrogen) and the UltraVision Quanto Detection System HRP DAB. Expression of E- and N-cadherin was semiquantitatively analyzed according to the cell percentage and stain intensity: 0 (0-10%); 1+ (11-30%); 2+ (31-70%); 3+ (&gt; 70%). Expression was considered positive if the score was ≥2. Pearson's χ² test and Spearman's correlation coefficient were used for statistical analysis. Results: The maximum staining for E-cadherin was observed in the control group (in 73%), for N-cadherin - in the main group (in 59%). Median expressions of E- and N-cadherin differed: in the control group, 70 [40-78] and 26 [0-40]; in the main group, 47 [45-60] and 59 [27-65]. Pearson's chi-squared test showed that patients with E-cadherin+ tumors (p = 0.006) statistically significantly prevailed in the control group, and patients with N-cadherin+ tumors (p = 0.027) prevailed in the main group. However, when considering the correlation between E-cadherin and N-cadherin in the groups, no statistically significant differences were found (rs = -0.042 in the control group and rs = 0.250 in the main group at p &gt; 0.05), apparently due to the limited sample. Conclusions: The immunohistochemical study revealed a tendency towards loss of E-cadherin and increased expression of N-cadherin, which is often associated with poor prognosis.
PD-1 blockade boosted chemo-target therapy in cT4NxM0 pMMR/MSS colorectal cancer.
Authors: Jun Huang, Fengyun Pei, Wan He, Yinghua Duan, Tianhao Shi, Yandong Zhao, Huabin Hu, Shuai Liu, Haiyang Chen, Fang He, Tingzhi Liu, Jiaoting Chen, Yijia Zheng, Xiaochun Meng, Heping Li, Xiaofang Guo, Yaoxu Chen, Mengli Huang, Jianping Wang, Meijin Huang
Journal: Journal of Clinical Oncology (2022)

e15606 Background: Immune checkpoint inhibitors (anti-PD-1 antibodies) have been testified good response in DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancers (CRC), while DNA mismatch repair-proficient/microsatellite stable(pMMR/MSS) CRCs, accounting for 85% of all CRCs, display poor response. Effective combined therapies for pMMR/MSS are needed for patients with local advanced colorectal cancers. Methods: In this pilot study, we administered 6 preoperative doses of anti-PD-1 antibody Sintilimab and Oxaliplatin and 5-FU/CF (mFOLFOX6) combined with Bevacizumab (only 5 doses in order not to delay surgery) in patients with cT4NxM0 colon or upper rectal cancers. Sintilimab (at a fixed dose of 200mg) was administered intravenously every 2 weeks, with surgery planned approximately 12 weeks after the first dose. The primary end point was pathological complete response(pCR). We also evaluated the major pathological response, radiological and pathological regression, safety, tumor mutation burden and tumor microenvironment (TME) molecules. Results: As of data cutoff (Dec 31,2021), median follow-up was 4.5 months (IQR 1.5-9.4). All patients underwent R0 surgical resection without treatment-related surgical delays. Of the 18 tumors that were removed, 18 were completely resected. A pCR occurred in 10 of 18 resected tumors (56%) and a major pathological response (MPR, ≤10% residual viable tumor) in 14/18(78%). At data cutoff, 18 were alive and 17 were free of recurrence. Treatment-related adverse events of grade 3 or higher occurred in 10% of the patients. Among the pCR tumors, two were found to harbored POLE mutation. The degree of pathological regression was deeper than radiological tumor shrinkage. The expression of CD3+ or/and CD3+/CD4+ stroma around tumor in pretreated tissue was significantly lower when comparing pCR and non-pCR (both p= 0.024). Conclusions: Neoadjuvant Sintilimab combined with Bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery and lead to a striking 56% and 78% complete and major pathological response. Stroma down-regulation of CD3 or CD3/CD4 expression was related to pCR.
Pain management in oncology-dedicated and general emergency departments.
Authors: Ilit Turgeman, Salvatore Campisi-Pinto, Maher Habiballah, Gil Bar-Sela
Journal: Journal of Clinical Oncology (2022)

e24076 Background: Cancer-related pain constitutes a dominant reason for admission to emergency services, and a significant patient and healthcare challenge. Evidence points to the rising prevalence of opioid misuse in this patient group. We sought to compare drug delivery in an oncology-dedicated emergency department (OED) and a general emergency department (GED) within the same hospital. Methods: Electronic files of patients with cancer seeking emergency services in a three-month period were obtained from the hospital registry. Data on patient demographics and drug-related characteristics were determined. Drug administration was compared between groups and thereafter according to admission types, using Fisher’s exact test, chi-square test and Mann-Whitney test. Results: In total, 584 patients had 922 visits to emergency services (OED n = 479; GED n = 443), and were administered 1815 drugs (OED n = 825; GED n = 990). Patient demographics and admission types were balanced between groups. Pain was the most common chief complaint (17% OED; 21% GED). In the OED, 12.5% of drugs were direct analgesics, compared with 19% in the GED. Opioids were prescribed more often in the GED than the OED (p = 0.008), significant for both pain related and non-pain related admissions, notably gastrointestinal and infectious conditions. Treatment in the GED was associated with delivery of three times as many intravenous opioids (p &lt; 0.001), a narrower spectrum in selection of oral and intravenous opioids (p = 0.003) and non-opioid analgesics, lower usage of pain adjuvants and rapid-acting opioids (p = 0.003), and finally, the administration of agents not recommended for cancer pain treatment, such as meperidine and benzodiazepines (p = 0.003). Similar utilization of resuscitative fluids, gastrointestinal agents and antiemetics was observed between groups, with larger variation in drug choice in the OED (p = 0.001). The OED showed greater usage of bisphosphonates and growth factors; conversely, antibiotics, blood products, clotting agents, antihypertensive and diabetic drugs, predominated in the GED. Conclusions: Compared to the GED, management of cancer-related pain in the OED is characterized by fewer opioids, enhanced diversity in drug type, route and method of delivery. Emergency services should be incorporated in cancer programs to promote safe and effective urgent care.
Meta-analysis of rates and causes of local recurrence in surgically-resected NSCLC and differences in recurrence and survival between Asian and non-Asian populations.
Authors: John M. Varlotto, Cristina Bosetti, Dwight Bronson, Claudia Santucci, Maria Vittoria Chiaruttini, Marco Scardapane, Gerald Hodgkinson
Journal: Journal of Clinical Oncology (2022)

e20579 Background: Recently, the PORT-C (China) and Lung ART (Europe) trials have been reported for non-small cell lung cancer patients (NSCLC) with surgically resected N2 nodal disease subsequently randomized to post-operative radiation (PORT). The two studies noted widely different locoregional relapse (LR) rates in the control arms, 18.3% in PORT-C and 28.1%(46% of recurrences) in Lung ART. We performed a meta-analysis of patients with N0-N2 disease to better understand risk factors for LR, and the possible differences in risk and rates between Asian (AP) vs. non-Asian populations (NAP). Methods: The present systematic review and meta-analysis identified all original studies of curative NSCLC surgical resections which reported risk and rates of LR between January 1st, 2000 and January 10th, 2021. Studies were excluded if patient number was less than 10, if metastatic disease was present, or if any neo-adjuvant chemotherapy and/or radiation was given. Eighty-seven studies were included; of these, 56 were of high quality (HQ) based on the Newcastle-Ottawa Scale (ratings 7-9). For each risk factor, we derived pooled relative risk (RR) and rate estimates using random-effects models. Results: Overall, the three highest pooled RRs for LR were N2 vs. N0 (RR 3.01), lymphovascular invasion (LVI; 1.92), and advanced T stage (T3-T4) vs. T1 (1.86). For HQ studies, the highest RRs for LR were LVI (1.94), sublobar vs. lobar resection (1.86), and N1 vs. N0 (1.84), but N2 vs N0 was no longer significant (RR 3.0 (95% confidence interval 0.57 -15.61) based on only 2 studies. The RRs for LR were consistent for most factors across geographic areas, although the RRs for male vs. female sex were higher in AP (1.44) than in NAP (1.09). The pooled rate of LR at 5-years was lower in the AP 12.00% (6.92-17.09) vs. NAP 22.66% (17.06 - 28.26), despite similar overall recurrence rates (both LR and distal) at 5 years in both populations: 38.03% (25.15-50.90) in AP and 37.30% (32.44-42.17) in NAP. However, a lower 5-year mortality rate was noted in AP (24.30%, 15.56 -33.03) than in NAP (45.87%, 41.23-50.50). Conclusions: Our meta-analysis found that N2 nodal disease is not a risk factor for LR when considering HQ studies based upon scant data, and confirmed that LR is lower in AP. We propose that prospective evaluation of LR risk factors and rates should be undertaken prior to any other prospective evaluation of PORT because LR may not be dependent upon N2 node status and because LR rates may differ in AP.
The prognostic value of genetic alterations of gasdermin (GSDM) family genes in breast cancer.
Authors: Zhenyu Ding, Tanxiao Huang, Juan Chen, Jinping Gao, Jiangjie Yang, Ming Liu, Yuanyuan Liu, Shifu Chen, Ying Piao
Journal: Journal of Clinical Oncology (2022)

e13006 Background: Breast cancer (BC) is the most commonly diagnosed cancer in 2021, with an estimated 2.9 million new cases (31%) and the second leading cause of cancer death in women. Gasdermins are encoded by six paralogous genes: GSDMA, GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5) and DFNB59 (also known as pejvakin, PJVK). They play a key role in pyroptosis. Few studies addressing the association between genetic alterations in the GSDM family genes and breast cancer prognosis have been reported up to now. Methods: We used a public cancer research platform named cBioPortal to analyze a cohort of 1983 breast cancer samples. We defined overall survival (OS) as the time between the procedure date when the tumor specimen was collected and the date of death or last follow-up visit. We compared the survival curves of two groups using Kaplan-Meier method and log-rank tests. The statistical significance level was set to 5% (p &lt; 0.05). Results: These genes were found in 685 (34.5%) samples with various genetic alterations, including missense mutation, splice mutation, truncating mutation, structural variant, amplification, deletion. GSDMC was the most frequently altered gene (18%), followed by GSDMD (17%), GSDMB (11%), GSDMA (10%), GSDME (2.5%), and PJVK (0.7%). Based on the result, patients were divided into the GSDM mutation and non-GSDM mutation group. The median OS of the GSDM mutation group was 124.57 months (Table), which is significantly shorter than the OS of the non-GSDM mutation group (log-rank test p = 5.64e-7). Conclusions: To our best knowledge, this analysis is the first investigation to evaluate the association between prognostic value and genetic alterations in GSDM family genes in breast cancer patients. Our investigation shows that genetic alterations in GSDM family genes can be used to predict poor prognosis in breast cancer patients. Further studies are warranted to verify and expand on these findings.[Table: see text]
LGG-36. Analysis of BRAF-related mutations in pediatric low-grade glioma
Authors: Shaoqun Li, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Most pediatric low-grade gliomas (pLGGs) are driven by a single genetic event resulting in up-regulation of the RAS/MAPK pathway. BRAF-related mutations are the most freauent molecular alteration in the pathway. To explore BRAF-related mutations in pediatric low-grade glioma is helpful for clinical practice. METHODS: In this study, patients with low-grade glioma aged ≤18 years in Guangdong Sanjiu Brain Hospital were enrolled. All patients accepted the tests of BRAF-related mutations with tumor tissue by next-generation sequencing (NGS). Results: A total of 26 patients diagnosed low-grade glioma and underwent NGS detection were included in this study. The male to female ratio was 6:7, and the median age was 9.5 years. 8 patients had tumors located in the cerebral hemisphere, 6 in the third or fourth ventricle, 5 in the cerebellum, 4 in the optic pathway, and 3 in the brain stem. A total of 14 patients took BRAF-related mutations, such as BRAF-KIAA1549 fusion, BRAF p.V600E mutation and other fusion. BRAF-KIAA1549 fusion was detected in 7 patients with pilocytic astrocytoma or pilomyxoid astrocytoma. BRAF p.V600E mutation was detected in 6 patients, two of whom were pleomorphic xanthoastrocytoma. A rare genetic fusion, BCAS1-BRAF fusion, was detected in 1 patient who had brain stem ganglioglioma. Among the 26 patients, 2 patients without BRAF-related mutations had typical multiple cafe-au-lait macules and were diagnosed as NF1-pLGG. These patients were treated with surgery, radiation, chemotherapy and targeted therapy. Only 2 patients received targeted therapy by Trametinib, Vimofinib and Everolimus after progression of the tumor. However, due to the severity of the disease, they eventually died. CONCLUSIONS: More than half of pLGG patients have BRAF-related mutations, which have the opportunity for targeted therapy. However, the optimal timing of targeted therapy still needs further exploration.